Induction of γ-Interferon by Avarol in Human Peripheral Blood Lymphocytes

Abstract

Avarol is a cytostatic and anti-human immunodeficiency virus (HIV) agent. In this study, the avarol caused induction of .gamma.-interferon (IFN-.gamma.) in buffy coat cells (human peripheral blood lymphocytes) is demonstrated by immunological and molecular biological techniques. IFN-.gamma. production was detected after a 24-hr incubation period with avarol; maximal production was obtained after 5 days in the presence of the optimal avarol concentration of 0.75 .mu.g/ml. Blotting experiments using human IFN-.gamma. cDNA and .beta.-actin cDNA containing plasmids showed that in the absence of avarol no IFN-.gamma. transcripts were present in lymphocytes. Already after a 24-hr incubation with avarol, IFN-.gamma. gene induction was detected, and maximal induction was found after a 5-day incubation period. The enhanced IFN-.gamma. production seems to be caused by a change at the transcriptional and/or post-transcriptional level, but not during subsequent nucleocytoplasmic transport of mRNA. This molecular event is specific, at least in relation to the expression of the .beta.-actin gene. Our studies demonstrate that avarol displays, besides its potential anti-tumour and anti-HIV activity, a potential immunomodulating effect.